Astrocyte-elevated gene-1 (AEG-1) has been reported to be associated with cancer progression in various types of human cancers, including liver cancer. However, to date, the molecular mechanism of AEG-1 action on the growth of liver cancer cells has been poorly elucidated. The present study aimed to investigate the effect of AEG-1 on the proliferation and apoptosis of liver cancer cells and the role of IL-6 in this process using the HepG2 human hepatoma cell line. shRNAs targeting AEG-1 were used to silence the expression of AEG-1. The effects on cell growth were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, colony formation and cell cycle assays. Apoptosis was analyzed by flow cytometry. The expression of IL-6 was examined by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, and the phosphorylation of Stat3 was detected by western blotting. AEG-1 knockdown was observed to induce cell proliferation inhibition and apoptosis through the suppression of IL-6 secretion. Stat3, a downstream target of IL-6 signaling, was suppressed in the AEG-1-silenced cells and target genes, including Bcl-2 and crystalin, αB, which are associated with cell survival, were downregulated. Overall, the findings suggest that aberrant AEG-1 expression promotes the growth of HepG2 liver cancer cells, contributing to the progression of liver cancer, which may partly be mediated by IL-6 signaling.